Dissociation between the renal and blood acid-base actions of acetazolamide in restraint-stressed rats.
Subcutaneous injection of acetazolamide (50 or 200 mg/kg) markedly increased the blood H+ and lowered the HCO3- concentrations in a dose-related manner. The urinary pH and HCO3- excretion were elevated. Restraint stress normalized the blood HCO3- levels but not the H+ concentrations; the high levels of urinary pH and the HCO3- content were unaffected in the acetazolamide-treated animals. These findings suggest that acetazolamide induces metabolic acidosis which appears not to be caused by depletion of blood HCO3- through increased urinary HCO3- excretion. Instead, an extra-renal mechanism could be responsible for the increased blood H+ concentration. Restraint stress significantly decreased the respiratory rate, which was prevented by acetazolamide pretreatment. The reversal of restraint-stress-induced respiratory depression by acetazolamide is probably due to the activation of both peripheral and medullary chemoreceptor sites by acidosis.
Cho
C H
CH
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Ogle
C W
CW
D000086:Acetazolamide / Q000494:pharmacology*; D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism*
D001639:Bicarbonates; D000086:Acetazolamide